Lupus autoimmunity frequently presents with neuropsychiatric manifestations, but underlying etiology remains poorly understood. Human brain cytoplasmic 200 RNA (BC200 RNA) is a translational regulator in neuronal synapto-dendritic domains. Here, we show that a BC200 guanosine-adenosine dendritic transport motif is recognized by autoantibodies from a subset of neuropsychiatric lupus patients.
View Article and Find Full Text PDFThe etiology of the autoimmune disorder systemic lupus erythematosus (SLE) remains poorly understood. In neuropsychiatric SLE (NPSLE), autoimmune responses against neural self-antigens find expression in neurological and cognitive alterations. SLE autoantibodies often target nucleic acids, including RNAs and specifically RNA domains with higher-order structural content.
View Article and Find Full Text PDFFragile X premutation disorder is caused by CGG triplet repeat expansions in the 5' untranslated region of FMR1 mRNA. The question of how expanded CGG repeats cause disease is a subject of continuing debate. Our work indicates that CGG-repeat structures compete with regulatory BC1 RNA for access to RNA transport factor hnRNP A2.
View Article and Find Full Text PDFTurnover of mRNA is a critical step that allows cells to control gene expression. Endoribonucleases, enzymes cleaving RNA molecules internally, are some of the key components of the degradation process. Here we provide a detailed characterization of novel endoribonuclease SLFN14 purified from rabbit reticulocyte lysate.
View Article and Find Full Text PDFZh Vyssh Nerv Deiat Im I P Pavlova
April 2015
The article concerns study of effects of polyclonal antibodies to serotonin-modulating anticonsolidation protein (SMAP) being in direct dependence on serotonin level and providing intracellular transduction of serotonergic signal, on positive reinforcement effect of morphine in rats. The task was formed in Wistar male rats in the model of morphine self-administration as a result of pressing of one of two levers attached to the wall, joined to the pump delivering each time 100 μg of morphine directly into the vena jugularis. In the 1st series of studies brain cingulate cortex and hypothalamus were taken from the rats achieved stable level of morphine intake and SMAP level was measured with indirect immune-enzyme assay.
View Article and Find Full Text PDFIn neurons, translational regulation of gene expression has been implicated in the activity-dependent management of synapto-dendritic protein repertoires. However, the fundamentals of stimulus-modulated translational control in neurons remain poorly understood. Here we describe a mechanism in which regulatory brain cytoplasmic (BC) RNAs cooperate with eukaryotic initiation factor 4B (eIF4B) to control translation in a manner that is responsive to neuronal activity.
View Article and Find Full Text PDFA key determinant of neuronal functionality and plasticity is the targeted delivery of select ribonucleic acids (RNAs) to synaptodendritic sites of protein synthesis. In this paper, we ask how dendritic RNA transport can be regulated in a manner that is informed by the cell's activity status. We describe a molecular mechanism in which inducible interactions of noncanonical RNA motif structures with targeting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 form the basis for activity-dependent dendritic RNA targeting.
View Article and Find Full Text PDFThe pathogenesis of inflammation in the central nervous system (CNS), which contributes to numerous neurodegenerative diseases and results in encephalopathy and neuroinflammation, is poorly understood. Sphingolipid metabolism plays a crucial role in maintaining cellular processes in the CNS, and thus mediates the various pathological consequences of inflammation. For a better understanding of the role of sphingosine kinase activation during neuroinflammation, we developed a bacterial lipopolysaccharide (LPS)-induced brain injury model.
View Article and Find Full Text PDFIn neurons, regulation of gene expression occurs in part through translational control at the synapse. A fundamental requirement for such local control is the targeted delivery of select neuronal mRNAs and regulatory RNAs to distal dendritic sites. The nature of spatial RNA destination codes, and the mechanism by which they are interpreted for dendritic delivery, remain poorly understood.
View Article and Find Full Text PDFBC1 RNA is a dendritic untranslated RNA that has been implicated in local translational control mechanisms in neurons. Prerequisite for a functional role of the RNA in synaptodendritic domains is its targeted delivery along the dendritic extent. We report here that the targeting-competent 5' BC1 domain carries two dendritic targeting codes.
View Article and Find Full Text PDFRNA localization is an important means of post-transcriptional regulation of gene expression in many eukaryotic cell types. In neurons, select RNAs are delivered to postsynaptic dendritic microdomains, a mechanism that is considered a key underpinning in the administration of long-term synaptic plasticity. BC1 RNA is a small untranslated RNA that interacts with translation initiation factors and functions as a translational repressor by targeting assembly of 48S initiation complexes.
View Article and Find Full Text PDFBrain Res Mol Brain Res
January 2005
Local protein synthesis in dendrites is thought to provide a mechanism for long-lasting modifications of synapses in response to physiological activity and behavioral experience. New synthesis of dendritic proteins may be triggered by various paradigms, including induction of epileptiform activity. Prerequisite for such modulated synthesis is a mechanism that limits translation of synaptodendritic mRNAs to times of demand.
View Article and Find Full Text PDFBC200 RNA, a small functional RNA that operates as a translational modulator, has been implicated in the regulation of local synaptodendritic protein synthesis in neurons. Cell type-specific expression of BC200 RNA is tightly controlled such that the RNA is not normally detected in somatic cells other than neurons. However, the neuron-specific control of BC200 expression is deregulated in a number of tumors.
View Article and Find Full Text PDFDespite the potentially important roles of untranslated RNAs in cellular form or function, genes encoding such RNAs have until now received surprisingly little attention. One such gene encodes BC1 RNA, a small non-mRNA that is delivered to dendritic microdomains in neurons. We have now eliminated the BC1 RNA gene in mice.
View Article and Find Full Text PDFIn neurons, local protein synthesis in synaptodendritic microdomains has been implicated in the growth and plasticity of synapses. Prerequisites for local translation are the targeted transport of RNAs to distal sites of synthesis in dendrites and translational control mechanisms to limit synthesis to times of demand. Here we identify dendritic BC1 RNA as a specific repressor of translation.
View Article and Find Full Text PDFIn neurons, localized RNAs have been identified in dendrites and axons; however, RNA transport in axons remains poorly understood. Here we analyzed axonal RNA transport in goldfish Mauthner neurons in vivo. BC1 RNA, a noncoding RNA polymerase III transcript that is targeted to dendrites in neurons of the rodent nervous system, was used as a probe for axonal RNA transport.
View Article and Find Full Text PDFBC1 RNA, a small non-coding RNA polymerase III transcript, is selectively targeted to dendritic domains of a subset of neurons in the rodent nervous system. It has been implicated in the regulation of local protein synthesis in postsynaptic microdomains. The gene encoding BC1 RNA has been suggested to be a master gene for repetitive ID elements that are found interspersed throughout rodent genomes.
View Article and Find Full Text PDFSeveral neuronal RNAs have been identified in dendrites, and it has been suggested that the dendritic location of these RNAs may be relevant to the spatiotemporal regulation of mosaic postsynaptic protein repertoires through transsynaptic activity. Such regulation would require that dendritic RNAs themselves, or at least some of them, be subject to physiological control. We have therefore examined the functional regulation of somatodendritic expression levels of dendritic BC1 RNA in hippocampal neurons in culture.
View Article and Find Full Text PDFIn nerve cells, a select group of RNAs has been localized to dendritic domains. Here we have examined dendritic RNA transport in sympathetic neurons in primary culture, using a microinjection protocol with neuronal BC1 RNA and with BC1-derived sequence segments. After cytoplasmic microinjection, full-length BC1 RNA was selectively transported to dendrites; in contrast, control RNAs such as nuclear RNAs and random-sequence irrelevant RNAs remained restricted to cytoplasmic areas proximal to the injection sites.
View Article and Find Full Text PDFIn this report it is suggested that at early stages of evolution ribosomes were responsible for synthesizing short oligonucleotide cDNA packets which formed the protogenic tandem repetitive sequences. Ribosomal RNA (rRNA) could have been the most probable template for such a synthesis. rRNA has homology with the monomers of tandem hypervariable repetitive elements of the genome.
View Article and Find Full Text PDFAs many as 63 infants with acute pneumonia, 7 children with ARVI (bronchiolitis) and 28 normal children were examined. At the height of the clinical manifestations there was an increase of the level of medium-weight molecules in blood serum, correlating well with the disease gravity determined by the intensity of the toxic syndrome. The highest concentration of serum medium-weight molecules was demonstrable in toxic and purulent complications due to acute pneumonia.
View Article and Find Full Text PDFMol Biol (Mosk)
January 1985
The ability of phycobilisomes (PBS) to photosensitize the reduction of methylviologen by dithiothreitol has been shown. This reaction has been studied in dependence on the structural integrity of PBS, nature and pH of the medium, and concentration of reagents. The action spectrum of the reaction has been measured, and its quantum yield has been detected.
View Article and Find Full Text PDFFluorescence emission and polarization spectra of the phycobilisomes (PBS) of the blue-green alga Nostoc muscorum were measured at 20, -73 and -196 degrees C while exciting at the absorption maximum of each pigment in the PBS. The emission spectra were deconvoluted into a number of Gaussian components and energy migration coefficients and quantum yields of fluorescence for the 8 forms of the phycobilins constituting the PBS were calculated. The overlap integrals and the critical and real distances for the energy transfer in the donor-acceptor pairs were evaluated.
View Article and Find Full Text PDFPhycobilisomes (PBS) isolated from Nostoc muscorum contain eight spectral forms of phycobiliproteins. PBS partially dissociated by osmotic or temperature shock, were separated into 42S and 34S particles by centrifugation in sucrose density gradient. The 42S particles are enriched with phycocyanin, the 34S ones--with allophycocyanin.
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